Lethal multiple pterygium syndrome, large cystic hygroma, and cleft palate: Rare and severe fetal presentations of RYR1- and NEB-related congenital myopathies.

Congenital myopathies are a genetically heterogeneous group of neuromuscular disorders that commonly present with congenital hypotonia and weakness but can also present broadly. The most severe presentation is neonatal with arthrogryposis and, rarely, fetal akinesia and pterygia, features also seen in lethal multiple pterygium syndrome (LMPS). We describe two fetuses with similar phenotype, including hydrops fetalis, large cystic hygromas, bilateral talipes, and fetal akinesia in the second trimester. Genetic diagnoses were made using exome sequencing. Both fetuses had a severe form of congenital myopathy. In the first fetus, we identified two novel compound heterozygous likely pathogenic variants consistent with autosomal recessive RYR1-related congenital myopathy (congenital myopathy 1B). In the second fetus, we identified two likely pathogenic variants, one of which is novel, likely in trans consistent with a diagnosis of autosomal recessive NEB-related congenital myopathy. Reaching a genetic diagnosis for these fetuses allowed the families to receive accurate genetic counseling for future pregnancies. These fetuses highlight the genetic and phenotypic heterogeneity of LMPS, and support a broad approach to genetic testing.

Absence of Ductus Venosus: A Comparison of 2 Distinctive Fetal Autopsy Cases and Embryologic Perspectives.

In fetal circulation, oxygenated blood from the placenta flows through the umbilical vein into the ductus venosus (DV), then enters the inferior vena cava, and subsequently reaches the right atrium of the heart. The DV serves as a shunt, allowing this oxygen-rich blood to bypass the liver. The absence of the DV (ADV), also known as agenesis of the DV, is a rare congenital anomaly. Without a DV, blood from the umbilical vein must follow alternative routes to the heart. In ADV cases, blood from the umbilical vein must follow 1 of 2 primary drainage patterns: either an extrahepatic shunt or an intrahepatic shunt. This report details the antenatal ultrasound and postmortem findings of 2 fetuses diagnosed with ADV by prenatal imaging studies. The first case involved a fetus with a persistent right umbilical vein connected directly to the suprahepatic IVC, accompanied by early obliteration of the left umbilical vein and true agenesis of the DV. This fetus also had additional congenital anomalies. In contrast, the second case involved a fetus with a normal left umbilical vein that entered the liver. However, despite an ultrasound diagnosis of "absence" of the DV, a DV was present, though markedly hypoplastic and probably minimally functional or non-functional. In this case, blood from the umbilical vein likely followed an alternate intrahepatic route through the portal and hepatic veins, before reaching the heart (intrahepatic shunt). These contrasting cases emphasize the heterogeneity of vascular anomalies and embryologic origins captured by the term "ADV." Additionally, the terminology of "absence" or "agenesis" may be misleading in some purported ADV cases. Specifically, in the second case, the DV was not absent; it was markedly hypoplastic instead. This also appears to be the first reported case of a hypoplastic DV in a fetus. Both cases underscore the importance of effective collaboration and clear communication between maternal-fetal medicine specialists and pathologists.

The Implementation of Preeclampsia Screening and Prevention (IMPRESS) Study.

BACKGROUND: Preeclampsia affects between 2% and 5% of pregnancies and is one of the leading causes of perinatal morbidity and mortality worldwide. Despite strong evidence that the combination of systematic preeclampsia screening based on the Fetal Medicine Foundation preeclampsia risk calculation algorithm with treatment of high-risk patients with low-dose aspirin reduces the incidence of preterm preeclampsia more than currently used risk-factor-based screening, real-world implementation studies have not yet been done in Canada. OBJECTIVE: This study aimed to assess the operational feasibility of implementing first-trimester screening and prevention of preterm preeclampsia (<37 weeks) alongside a publicly funded first-trimester combined screening program for aneuploidies. STUDY DESIGN: This was a prospective implementation study. Consecutive pregnant patients referred for first-trimester combined screening (11-13+6 weeks) were offered screening for preeclampsia based on the Fetal Medicine Foundation algorithm concomitantly with their aneuploidy screen. Consenting participants were screened using maternal risk factors, mean arterial pressure, uterine artery Doppler pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor. Risk for preterm preeclampsia (<37 weeks) was calculated using the Fetal Medicine Foundation algorithm, and individuals with a risk score ≥1 per 100 were recommended to use aspirin (162 mg once daily at bedtime, <16-36 weeks). Implementation metrics assessed included: acceptability, operational impact, proportion of aspirin initiation, quality and safety measures, and screen performance. RESULTS: Between December 1, 2020 and April 23, 2021, 1124 patients consented to preeclampsia screening (98.3% uptake), and 92 (8.2%) screened positive. Appointments for patients receiving first-trimester combined screening aneuploidy and preeclampsia screening averaged 6 minutes longer than first-trimester combined screening alone, and adding uterine artery Doppler pulsatility index averaged 2 minutes. Of the 92 patients who screened as high-risk for preeclampsia, 72 (78.3%) were successfully contacted before 16 weeks' gestation. Of these, 62 (86.1%) initiated aspirin, and 10 (13.9%) did not. Performance audit identified a consistent negative bias with mean arterial pressure measurements (median multiple of the median <1 in 10%); other variables were satisfactory. There were 7 cases of preterm preeclampsia (0.69%): 5 and 2 in the high- and low-risk groups, respectively. Screening detected 5 of 7 (71.4 %) preterm preeclampsia cases, with improved performance after adjustment for aspirin treatment effect. CONCLUSION: This study confirms the operational feasibility of implementing an evidence-based preeclampsia screening and prevention program in a publicly funded Canadian setting. This will facilitate implementation into clinical service and the scaling up of this program at a regional and provincial level.

Confirmation Testing of Essure Microinserts in Unintended Pregnancies Using a 10-Year Retrospective Database.

STUDY OBJECTIVES: To examine the imaging modality used in cases of Essure failures and determine the cause of the unintended pregnancies (noncompliance to follow-up recommendations, misinterpretation of the imaging test, or device failure). DESIGN: Retrospective, single-center interventional cohort (Canadian Task Force classification II-2). SETTING: Tertiary level hospital. PATIENTS: Women who have had Essure placement and subsequent pregnancy. INTERVENTIONS: Coding data from the Regina General Hospital was examined for any pregnancy occurring after an Essure procedure. The hospital charts were then reviewed for data collection. A separate imaging database established over the same time frame was then reviewed to determine the imaging modality used in each case (transvaginal ultrasound [TVU], hysterosalpingogram [HSG], or none). Results of the imaging study were reviewed and the cause of the failure determined. MEASUREMENTS AND MAIN RESULTS: Twenty-four pregnancies in 25 women were identified after Essure procedures from January 1, 2003 to March 31, 2013. There were 4 in vitro fertilization pregnancies and 4 pregnancies where the woman had been instructed not to rely on the devices because of incomplete placement noted at time of the procedure. Therefore, 17 unintended pregnancies occurred of a total 2080 procedures performed. Examination of the imaging studies revealed that 11 were due to patient noncompliance (either early cessation of backup contraception or failure to go for confirmatory imaging), 5 due to misinterpretation of the imaging tests (3 HSG, 2 TVU), and 1 device failure. This reveals a cumulative failure rate of 6 of 2080 or .29% over 10 years with only .04% (1/2080) being device related. CONCLUSION: Essure sterilization is an effective means of permanent contraception with a device failure rate of only .04%. Most unintended pregnancies after the Essure procedure result from a failure to comply with follow-up recommendations, and strategies to improve compliance should be emphasized.

Essure microinsert imaging: does abnormal shape on ultrasound predict complications on HSG?

OBJECTIVE: We hypothesize that the shape of the Essure microinsert on ultrasound is able to predict complications evident on hysterosalpingogram (HSG), the accepted gold standard. METHOD AND MATERIALS: From July 2, 2009 to July 2, 2012, 441 women at our institution received Essure microinsert placement for the purpose of permanent sterilization. 2D and 3D coronal plane transvaginal ultrasounds were performed three months after Essure microinsert placement. Those patients with complications identified on ultrasound, a non-diagnostic ultrasound, or following a difficult insertion were referred for HSG. Patients with both HSG and ultrasound performed were retrospectively selected and anonymized. The ultrasounds were reviewed by a single, blinded radiologist. A total of 122 microinserts in 65 patients were described on ultrasound using a numeric grading system and compared to HSG findings. RESULTS: Microinsert placement resulted in 37 complications, 31 of which were identified on ultrasound, including uterine and tubal perforations and placement in the endometrial cavity. The sensitivity of Essure microinsert shape on ultrasound in predicting complications, compared with standard HSG, was 94%, with a positive predictive value of 85%; specificity was 95%, with a negative predictive value of 98%. The Kappa coefficient was 0.85 (p < 0.001). CONCLUSION: Our results suggest that ultrasound may be used as a frontline imaging modality for patients after Essure microinsert placement.

Outcomes in the ultrasound follow-up of the Essure micro-insert: complications and proper placement.

OBJECTIVE: To review the use of three-dimensional ultrasound follow-up of the Essure micro-insert placement at three months for the identification of misplaced coils and complications. METHODS: We conducted a retrospective cohort study of reproductive age women requesting permanent sterilization in a tertiary care ambulatory women's clinic. Women who underwent placement of the Essure micro-insert were assessed for appropriate positioning of the Essure micro-insert coil using three-dimensional ultrasound as well as hysterosalpingography when indicated. RESULTS: A total of 610 women who had undergone the Essure procedure with ultrasound follow-up at three months were retrospectively reviewed and in 524 (86%) the location and shape were both normal. The remaining 86 (15%) required hysterosalpingography to confirm proper placement, 34 because of a non-diagnostic ultrasound and the remaining 52 for a complication noted on ultrasound, including perforation, proximal or distal migration of the device, or device expulsion. CONCLUSION: Ultrasound can be used at three months after Essure placement to identify normal placement as well as misplaced and perforated devices.

Postmortem computed tomography in a case of Apert Syndrome: correlation with conventional autopsy and prenatal ultrasound.

BACKGROUND: There have been very few small studies or case reports in the literature considering noninvasive postmortem imaging as supplement to autopsy, especially in fetuses with skeletal dysplasias. Apert syndrome accounts for 4.5% of all patients with craniosynostotic syndromes. It is classically characterized by the triad of coronal craniosynostosis, midfacial hypoplasia, and symmetric bony syndactyly of the hands and feet. PURPOSE: Illustrate the accuracy of a postmortem computed tomography compared with a conventional autopsy as well as review common imaging findings in a case of prenatally diagnosed Apert syndrome. CASE: A 31-year-old woman was seen for a routine prenatal ultrasound. A craniofacial syndrome was suspected by prenatal ultrasound, and the anomalies raised the suspicion of Apert syndrome. After genetic counseling, it was chosen to terminate the pregnancy. A postmortem computed tomographic scan was performed, followed by a conventional autopsy that confirmed the findings. DISCUSSION: Computed tomography provides many advantages in postmortem assessment. Postmortem imaging cannot replace conventional autopsy but is superior in axial and appendicular skeleton assessment. These studies provide supplemental information that may guide the autopsy. In situations where the parents wish not to pursue an autopsy, postmortem imaging can provide useful clinical information.

Confirmation of Essure microinsert tubal coil placement with conventional and volume-contrast imaging three-dimensional ultrasound.

OBJECTIVE: To determine the accuracy of ultrasound in the assessment of proximal fallopian tube positioning of the Essure microinsert coil 3 months after postprocedure. DESIGN: Prospective cohort study (Canadian Task Force classification II-2). SETTING: Reproductive-age women in a tertiary care hospital. PATIENT(S): Reproductive-age women presenting with a request for permanent contraception. INTERVENTION(S): Hysteroscopic sterilization with the Essure microinsert coil and conventional or volume-contrast three-dimensional (3D) ultrasound imaging 3 months after the procedure. MAIN OUTCOME MEASURE(S): Coil position on ultrasound. RESULT(S): Forty-eight of the 50 patients had successful placement of the Essure coils, and three patients required a second attempt on one tube. Conventional or volume-contrast (3D) ultrasound showed proper positioning of the coils within the proximal fallopian tube in 42 women (84%); five women (10%) required hysterosalpingogram to show appropriate positioning. Two patients (4%) required laparoscopic tubal sterilization, and one patient (2%) was lost to follow-up. CONCLUSION(S): Transvaginal ultrasound is an acceptable method of confirming proper placement of the Essure microinsert coil within the proximal fallopian tube 3 months after the procedure.